There are two studies that provide the data for this project. CARDIA. The CARDIA Study is a prospective, epidemiologic investigation of the determinants and evolution of cardiovascular risk factors among 5,115 African American and white young adults 18-30 years of age at baseline in 1985-86. Participants were recruited from the populations of four geographic locations (Birmingham, AL; Chicago, IL; Minneapolis, MN; and Oakland, CA). The CARDIA Coordinating Center is also located at the University of Alabama-Birmingham. The study population was approximately balanced according to sex (54% women), ethnicity (52% African American), and education (40% with less than equal to 12 years of education) at each center. After the 1984 baseline, 7 additional examinations were undertaken. In 2010 the CARDIA Brain MRI study was added to the 25-year follow-up exam, and in 2015 the MRI was repeated in the same people. The purpose of this study is to conduct a novel, detailed investigation of the earliest physiologic and morphologic phases of brain disease process in a community-based middle age cohort. This information could prove critical in prevention and early management of CVD, before irreversible damage and functional consequences occurs. AGES- Reykjavik is a population-based follow up study of men and women born 1907-1934. The cohort was established in 1967 by the Icelandic Heart Association; participants were followed up to six times. To advance our understanding of genetic and non-genetic risk factors, AGES- Reykjavik focuses on obtaining high quality quantitative measures of intermediate components of major diseases of old age. To this end, extensive bio-image and bio-specimen phenotype measures have been made of multiple physiological systems, including neurocognitive, vascular, musculoskeletal, and body composition, and metabolic measures. Together these studies have unique and rich data on brain function and structure, including measures of cognition, structural and physiologic measures of the brain, and depression. We are currently conducting Genome Wide Association studies (GWAS) of endophenotypes including cognition, and regional brain tissue volumes, as well as investigating the predictiveness of genetic risk scores for clinical and sub-clinical brain disease.